Rift Valley fever virus — Questions

• Heavy rainfall: prolonged rains, often in an El Nino year, flood shallow depressions (dambos).
• Mosquito hatching: flooding hatches Aedes eggs already carrying the virus through transovarial transmission.
• Livestock amplification: the virus amplifies in sheep, cattle and goats, producing abortion storms that act as a sentinel.
• Secondary vectors: Culex and other mosquitoes amplify transmission further.
• Human spillover: people are infected by mosquito bites and by contact with infected animal tissues at slaughter, veterinary work or nursing sick animals.

Only about 1% to 2% of infections progress to severe disease; the great majority are a self-limiting febrile illness.

Severe disease is uncommon, but the scale of epizootics still yields many such cases.

RVFV shows only about 4% to 5% nucleotide diversity among strains since the 1970s and behaves as a single antigenic type, so one well-matched vaccine can protect broadly.

It does not undergo antigenic shift or drift into escape serotypes.

Because viraemia is high in the acute phase, reverse-transcription polymerase chain reaction (RT-PCR) and immunoglobulin M (IgM) capture ELISA on blood are the mainstays, supported by virus isolation and paired serology.

RVF is mosquito-borne, so there is no tick to identify.

Although mosquitoes drive the animal epizootic, most people are infected by direct contact with the blood or tissues of infected livestock, during slaughter, birthing and the handling of aborted material.

Mosquito bite is a lesser route, and there is no person-to-person spread.

Gn and Gc are arranged as an ordered icosahedral lattice on the lipid envelope, a more regular surface than the pleomorphic nairoviruses, and there is no matrix protein.

The genome exists as a ribonucleoprotein, not an icosahedral capsid.

Retinitis typically develops one to three weeks after the initial symptoms, sometimes after the fever has settled, and where it involves the macula it can cause permanent visual loss.

RVFV is a phlebovirus in the family Phenuiviridae, order Bunyavirales.

Nairoviridae (Crimean-Congo haemorrhagic fever) and Hantaviridae are the other bunyavirus families of note; filoviruses and flaviviruses are unrelated.

Daubney and Hudson described the disease from an outbreak of abortions and lamb deaths on a farm in Kenya’s Rift Valley, naming it enzootic hepatitis.

The Egyptian, Congo and Crimean events belong to other viruses or to much later outbreaks.

RVFV is highly infectious by aerosol, which caused many laboratory-acquired infections before modern biosafety practice, and is one reason it is handled under enhanced containment.

It does not spread from patient to patient by droplets.

There is no licensed human RVF vaccine; the most advanced candidate, ChAdOx1 RVF, was safe and immunogenic after a single dose in a phase 1 trial and is designed for both livestock and people.

Older inactivated preparations have protected only small numbers of laboratory and veterinary workers.

In 2000 RVFV appeared in Saudi Arabia and Yemen, its first confirmed spread beyond Africa, probably carried across the Red Sea in infected livestock.

Egypt and Madagascar are within Africa, and the Indian and European events did not occur.

The haemorrhagic-hepatic form is the most lethal, with a case fatality of up to around 65%.

The milder febrile illness that most patients experience has a very low mortality.

The incubation period is short, usually 2 to 6 days, after which most people have a brief self-limiting fever.

The longer intervals describe other infections.

The liver is the main target and hepatic necrosis is the central lesion of severe RVF, reflected in steeply raised transaminases and, in the worst cases, jaundice and liver failure.

Renal failure occurs but is usually secondary.

NSs is the dominant virulence factor: it suppresses the type I interferon response, shutting down host-cell transcription and blocking interferon-beta induction.

The polymerase, glycoproteins and nucleocapsid are separate gene products.

Most infections are an abrupt, often biphasic influenza-like illness with fever, myalgia, arthralgia and headache, sometimes with photophobia and neck stiffness that can mimic meningitis, resolving over four to seven days.

Because livestock amplify the virus and are the main source of human infection, vaccinating animals is the most effective way to protect people, the logic of One Health.

Patients are not infectious to others, and mosquito eradication is not feasible during floods.

The RVFV small (S) segment is ambisense, encoding the nucleocapsid protein in one orientation and the non-structural NSs from the opposite-sense strand.

The genome is otherwise negative-sense, tripartite RNA, not DNA, positive-sense, circular or unsegmented.

A failure to mount an early type I interferon response is linked to severe and fatal disease, and those who die often fail to make RVFV-specific antibody.

A brisk innate response followed by neutralising antibody is the correlate of protection.

Treatment is supportive; unlike for Crimean-Congo haemorrhagic fever, ribavirin is not recommended for RVF, having been linked to late-onset encephalitis in animal studies, and corticosteroids are not recommended either.

No antiviral is approved for the disease.